Reactive oxygen species (ROS) play a crucial role in the pathogenesis of cardiovascular diseases. However, vascular-derived hydrogen peroxide (H2O2) also serves as an important signaling molecule in the cardiovascular system at its low physiological concentrations. At low concentrations, H2O2 can act as a second messenger, transducing the oxidative signal into biological responses through posttranslational protein modification. These structural changes ultimately lead to altered cellular function. The intracellular redox status is closely regulated by the balance between oxidant and antioxidant systems, and their imbalance can cause oxidative or reductive stress, leading to cellular damage and dysregulation. For example, excessive H2O2 deteriorates vascular functions and promotes vascular disease through multiple pathways. The RhoA/Rho-kinase pathway plays an important role in various fundamental cellular functions, including the production of excessive reactive oxygen species (ROS), leading to the development of cardiovascular diseases. Rho-kinase (ROCK1 and ROCK2) belongs to the family of serine/threonine kinases and is an important downstream effector of the small GTP-binding protein RhoA. Rho-kinase plays a crucial role in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension (PH), stroke, and heart failure. Thus, Rho-kinase inhibitors may be useful for the treatment of cardiovascular diseases in humans. Furthermore, cyclophilin A (CyPA) is secreted from vascular smooth muscle cells, which augments the destructive effects of ROS. Thus, it is important to understand the H2O2 signaling and the roles of downstream effectors such as CyPA in the vascular system in order to develop new therapeutic strategies for cardiovascular diseases. In this chapter, we will discussthe dual roles of vascular-derived H2O2 in mediating vascular functions (physiological roles) and promoting vascular diseases (pathological roles).
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)